Quaternary ammonium salts of diisopropylaminoalkyl esters of diphenylacetic acid



Patented Aug. 11, 1953 UNITED STATES QUATERNARY AMMONIUDISALTS .QFJIIISO- PROPYLAMINOALKEZEL ESTERS OF DI- .PHENYLACETIC ACID Richard A.'-Robinson, Morton Grove, Ill., assignor to 6-D. Seal-1e 85120., Chicago, 111., a corporation- (if-Illinois N Drawing. Application February 24,1950, Serial No. 146,147

3 Claims. (Cl. 260-469,)

' Pressures during vacuum distillation are measured in millimeters (mm.) of mercury.

Example 1 A mixture of 16.3 g. of diisopropylaminoethyl chloride, 21 g. of diphenyl acetic acid and 100 ml. of isopropanol is heated at reflux temperature for 2 hours and then vacuum distilled at 30 mm.

To obtain the free base of the beta-diisopropyl- CH3 CHCHI aminoethyl ester of diphenyl acetic acid one extracts with water, treats with aqueous potassium carbonate and extracts with ether. The ether OH OH solution is dried over sodium sulfate and then oHi over potassium carbonate. The ether is again l5 removed at 30 mm. pressure and the residue, gl zgllllfgvgigniso? iolwggizllzylene group an X which weighs 32 gm, distilled at 0.05 mm. pressure. The ester distils at 153 without evidence amylene groups f A may represent of decomposition, g. of pure material being are bivalent, saturated, aliphatic hydrocarbon obtained The hydrochloride, Obtained by treat i'f i 9 mm "9 elght *F 9 2o ment of the ether solution with alcoholic hydroese radicals are derived from straight-chained gen chloride, forms White crystals, which melt or branched-chained aliphatic hydrocarbons and at include such radicals as ethylene, propylene, butylene, amylene and polymethylene radicals Example 2 such as trimethylene, tetramethylene and related 35 g. of the beta-diisopropylaminoethyl ester of polymethylenes including octamethylene. diphenyl acetic acid, obtained by the method de- In the foregoing structural formula X is the scribed in Example 1, are stored with 23 g. of equivalent of an anion such as chloride, bromide, methyl bromide and 125 ml. of ethyl methyl iodide, sulfate, methyl sulfate, ethyl sulfate, phosketone in a closed system for 15 hours at 70. 13 phate, citrate, lactate, ascorbate, tartrate, beng. of white crystals of the diphenyl acetate of N- zenesulfonate and the like. (2 hydroxyethyl) N,N diisopropyl-N-methyl The compounds which constitute this invenammonium bromide separate. The crystals are tion show unusual therapeutic properties, espewashed with ethyl methyl ketone and dried at ciallyin their action inhibiting autonomic nervous 70; they melt at 176. The filtrate is treated function. Unlike the usual sympathicolytics, with 13 g. of additional methyl bromide and again such as N-(2-chloroethyl) dibenzylamine, 2- stored at for 18 hours, giving an additional benzyl-2-imidazoline and ergotamine, and para- 13 g. yield. If the filtrate is concentrated to sympathicolytics such as atropine and the bellaml. and again treated with 23 g. of methyl brodonna alkaloids, which act on the neuromuscular mide, 15 g. of additional crystals may be obtained. junction, the diphenylacetates which constitute In order to convert this bromide into the my present invention have a blocking effect on 40 citrate, one dissolves 3 mols of the bromide the sympathetic and parasympathetic impulses as they travel through the ganglia. Thus, the impulse actually never reaches the myoneural junction.

The examples below describe in detail certain of the compounds which comprise this invention and methods for producing them. However, this invention is not to be construed as limited thereby in spirit and in scope. To one skilled in the art it will be apparent that numerous modifications in methods and materials may be made without departing from the invention. In each of the following examples, temperatures are given in degrees centigrade, parts by Weight in grams (g.) and parts by volume in milliliters (ml.).

in absolute methanol and treats this solution with 1 mol of silver citrate and 2 mols of citric acid, filters and concentrates the solution by distilling at 30 mm.

Example 3 35 g. of diphenyl acetic acid and 32 g. of deltadiisopropylaminobutyl chloride are heated in ml. of isopropanol at reflux temperature for 3 hours and then distilled at 30 mm. The residue is treated with an aqueous solution of potassium carbonate and then extracted with diethyl ether. The ether solution is dried over potassium carbonate, the potassium carbonate filtered oil, and the filtrate distilled at 30 mm. to remove the ether. The residual oil consists mostly of deltadiisopropylaminobutyl diphenyl acetate.

Example 4 at 70. White crystals of the diphenyl acetic acid' ester of N (delta hydroxybutyl) N,N di-isopropyl-N-methyl-ammonium sulfate separate. By evaporation of the filtrate and addition of a further amount of methylating agent, one may obtain an additional yield.

I claim: 1. The compounds of the structural formula CHOOO-AlkN-CH(OH3)2.X

4 wherein Alk is an alkylene radical and wherein X is one equivalent of an anion.

2. The quaternary ammonium salts of B-diisopropylaminoethyl diphenylacetate of the general formula wherein X is one equivalent of an anion.

3. The halides of the diphenyl acetate of N- (beta-hydroxyethyl) -N,N-diisopropyl-N methyl ammonium of the general formula shown in claim 2 where X is a halide ion.

RICHARD A. ROBINSON.

References Cited in the file of this patent Jensen et al., Acta Chem. Scand, 2 381-383 

1. THE COMPOUNDS OF THE STRUCTURAL FORMULA IG-01 WHEN ALK IS AN ALKYLENE RADICAL AND WHEREIN X IS ONE EQUIVALENT OF AN ANION. 